CD163 Expression in Neurons After Experimental Intracerebral Hemorrhage

Stroke. 2017 May;48(5):1369-1375. doi: 10.1161/STROKEAHA.117.016850. Epub 2017 Mar 30.


Background and purpose: CD163, a receptor for hemoglobin, is involved in hemoglobin clearance after intracerebral hemorrhage (ICH). In contrast to microglial/macrophage CD163, neuronal CD163 hemoglobin has not been well studied. This study examined the expression of neuronal CD163 in a pig model of ICH and in vitro rat cortical neurons and the impact of deferoxamine on that expression.

Methods: There were 2 parts to this study. In the in vivo part, piglets had injection of autologous blood into the right frontal lobe. The time course of CD163 expression and the effect of deferoxamine on the expression of CD163 after ICH were determined in the grey matter. In the in vitro part, the levels of CD163 and neuronal death and the effect of deferoxamine were examined in rat cortical neurons culture treated with hemoglobin.

Results: CD163-positive cells were found, and the CD163 protein levels were upregulated in the ipsilateral grey matter after ICH. The CD163 levels peaked at days 1 and 3. The CD163-positive cells were colocated with NeuN-positive, heme oxygenase-2-positive, and terminal deoxynucleatidyl transferase dUTP nick end labeling-positive cells. Deferoxamine treatment attenuated ICH-induced CD163 upregulation and significantly reduced both brain CD163 and hemoglobin levels at day 3. Treating neuronal cultures with hemoglobin for 24 hours resulted in CD163 upregulation and increased cell death. Deferoxamine significantly attenuated the hemoglobin-induced neuronal death and CD163 upregulation.

Conclusions: CD163 is expressed in neurons and upregulated after ICH. Deferoxamine reduced ICH-induced CD163 upregulation and brain cell death in vivo and hemoglobin-induced CD163 upregulation and neuronal death in vitro.

Keywords: cell death; cerebral hemorrhage; deferoxamine; macrophages; swine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Brain / metabolism*
  • Cell Death
  • Cerebral Hemorrhage / metabolism*
  • Deferoxamine / pharmacology*
  • Disease Models, Animal
  • Hemoglobins / metabolism*
  • Neurons / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / metabolism*
  • Siderophores / pharmacology*
  • Swine
  • Up-Regulation


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Hemoglobins
  • Receptors, Cell Surface
  • Siderophores
  • Deferoxamine